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Sep 16, 2013
 |  BioCentury  |  Tools & Techniques

Conjugation for concentration

Synta's Hsp conjugates may deliver more payloads than ADCs, hit more cancers

Synta Pharmaceuticals Corp.'s Hsp90 inhibitor-drug conjugates may improve the therapeutic index of small molecule cancer agents by making them accumulate selectively in cancer cells. Synta thinks its products, dubbed HDCs, will reach higher concentrations in cancer cells than antibody-drug conjugates and thus can deliver effective doses of more types of cancer agents.

Synta last week disclosed it has synthesized more than 350 HDCs, including a portfolio of 18 it has made with marketed cancer agents.

The company expects to submit its first IND from the program in 18 months.

Each HDC is composed of a moiety that inhibits heat shock protein 90 (Hsp90), a cleavable linker and a payload molecule.

Hsp90 is a molecular chaperone protein that is expressed about two- to tenfold higher in tumor cells than in normal cells. Many of the proteins it assists are associated with oncogene addiction, resistance to chemotherapy and radiation therapy, angiogenesis or metastasis.

Oncogene addiction refers to a phenomenon in which tumors are highly sensitive to therapies targeting just one oncogene out of all the deregulated genes that could serve as potential targets (see SciBX: Science-Business eXchange, Nov. 3, 2011).

President and CEO Safi Bahcall said the idea for HDCs stemmed from the observations that all tumors grow in an Hsp90-dependent manner and...

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